25 research outputs found
Genomic investigations of unexplained acute hepatitis in children
Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children
Quantifying dissolved organic carbon concentrations in upland catchments using phenolic proxy measurements
Concentrations of dissolved organic carbon (DOC) in soil and stream waters in upland catchments are widely monitored, in part due to the potential of DOC to form harmful by-products when chlorinated during treatment of water for public supply. DOC can be measured directly, though this is expensive and time-consuming. Light absorbance in the UVâvis spectrum is often used as a surrogate measurement from which a colour-carbon relationship between absorbance and DOC can be derived, but this relationship can be confounded by numerous variables. Through the analysis of data from eight sites in England and Wales we investigate the possibility of using the concentration of phenolic compounds in water samples as a proxy for DOC concentration. A general model using data from all the sites allowed DOC to be calculated from phenolics at an accuracy of 81â86%. A detailed analysis at one site revealed that a site-specific calibration was more accurate than the general model, and that this compared favourably with a colour-carbon calibration. We therefore recommend this method for use where estimates of DOC concentration are needed, but where time and money are limiting factors, or as an additional method to calculate DOC alongside colour-carbon calibrations. Tests demonstrated only small amounts of phenolic degradation over time; a loss of 0.92 mg Lâ1 after 8 months in storage, and so this method can be used on older samples with limited loss of accuracy
MetExplore: collaborative edition and exploration of metabolic networks
Metabolism of an organism is composed of hundreds to thousands of interconnected biochemical reactions responding to environmental or genetic constraints. This metabolic network provides a rich knowledge to contextualize omics data and to elaborate hypotheses on metabolic modulations. Nevertheless, performing this kind of integrative analysis is challenging for end users with not sufficiently advanced computer skills since it requires the use of various tools and web servers. MetExplore offers an all-in-one online solution composed of interactive tools for metabolic network curation, network exploration and omics data analysis. In particular, it is possible to curate and annotate metabolic networks in a collaborative environment. The network exploration is also facilitated in MetExplore by a system of interactive tables connected to a powerful network visualization module. Finally, the contextualization of metabolic elements in the network and the calculation of over-representation statistics make it possible to interpret any kind of omics data